"Cancer progenitor cell markers" Phase I/II Fast-Track application In response to RFA-CA-08-011 "Innovative and Applied Molecular Analysis Technologies for Cancer (SBIR [R43/R44])" Circulating tumor cells (CTCs) have been identified in peripheral blood from patients with epithelial cancers. Recent studies suggest that CTCs could represent a potential alternative to biopsies as a source of tumor tissue for the detection, characterization and monitoring of non-hematologic cancers. However, current strategies for isolating CTCs are limited to complex analytic approaches based on epithelial cell surface markers. Since markers specific for cancer cells are lacking, the molecular identity of CTCs remains to be investigated. We postulate that the ability of cell adhesion matrix (CAM)-coated devices developed in Vitatex to isolate, characterize and propagate CTCs could lead to the identification of novel cancer stem or progenitor cell markers and expand the understanding of the mechanism of tumor progression and metastasis. To address this need, a panel of tumor progenitor cell markers upregulated in CTCs that were recently resolved by this team will be used to improve the CTC detection specificity and sensitivity in patients with epithelial ovarian cancer, as well as to evaluate the potential role of CTCs in ovarian tumor peritoneal metastasis. Initially we will select novel tumor progenitor and invasiveness markers and optimize a cell-based flow cytometry blood test by validating its performance using fluorescence microscopic imaging to improve the sensitivity and specificity of CTC detection. We will then develop a nucleic acid-based blood test using a focused panel of tumor progenitor cell markers in multigene quantitative PCR analysis to phenotype patients with ovarian cancer who are treated at the Stony Brook University Medical Center and to monitor treatment response. To evaluate the relevance of CTCs in metastatic progression, cells sorted by both CAM adhesion and expression of a tumor progenitor gene will be examined for their ability to progress into peritoneal, liver and lung metastases by using an experimental ovarian metastasis animal model. The commercialization objectives are to manufacture an efficient rare cell separation system as a research tool for molecular analysis of epithelial cancers in peripheral blood, and to develop a novel blood test product that allows more sensitive diagnostic and prognostic evaluation of cancer, particularly relating to its metastatic potential.